Linking Diet, Gut Microbiota and Autoimmunity: A Phytoestrogen Diet Alters the Gut Microbiota and Influences Experimental Autoimmune Encephalomyelitis (EAE)

Abstract The etiology of multiple sclerosis (MS) involves genetic predisposition and an unknown environmental trigger. The gut microbiome may be an environmental contributing factor. Previously, we have shown that certain gut bacteria especially those with ability to metabolize phytoestrogen are less abundant in MS patients compared to healthy individuals. We hypothesize that phytoestrogen metabolism via microbial flora induces an anti-inflammatory state in the intestine. Therefore their reduced levels might predispose to disease development and/or severity. To test this, we placed C57Bl/6 mice on a diet with or without phytoestrogens and induced Experimental Autoimmune Encephalomyelitis (EAE), an experimental model of MS. We observed that mice on a phytoestrogen diet developed milder disease compared to those on a phytoestrogen free diet; a phenomenon dependent on the presence of phytoestrogen-metabolizing bacteria in the gut. We also found that a phytoestrogen diet alters the gut microbiota compared to a phytoestrogen-free diet with the gut microbiota of phytoestrogen group closely resembling the gut microbiota of healthy individuals. The gut microbiota of mice on a phytoestrogen-free diet closely resembles the gut microbiota of MS patients. Furthermore, mice on a phytoestrogen-diet exhibit an altered immune profile in the colonic lamina propria and mesenteric lymph nodes. Finally, we found that phytoestrogen-metabolites altered the cytokine-producing function of human colonic epithelial cells in vitro. Our results suggest that dietary phytoestrogen metabolites produced by commensal bacteria can alter the phenotype and function of the intestinal immune system, which may influence central nervous system autoimmunity.